Document Detail


Rapid and extensive uptake and activation of hydrophobic triphenylphosphonium cations within cells.
MedLine Citation:
PMID:  18294140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondria-targeted molecules comprising the lipophilic TPP (triphenylphosphonium) cation covalently linked to a hydrophobic bioactive moiety are used to modify and probe mitochondria in cells and in vivo. However, it is unclear how hydrophobicity affects the rate and extent of their uptake into mitochondria within cells, making it difficult to interpret experiments because their intracellular concentration in different compartments is uncertain. To address this issue, we compared the uptake into both isolated mitochondria and mitochondria within cells of two hydrophobic TPP derivatives, [3H]MitoQ (mitoquinone) and [3H]DecylTPP, with the more hydrophilic TPP cation [3H]TPMP (methyltriphenylphosphonium). Uptake of MitoQ by mitochondria and cells was described by the Nernst equation and was approximately 5-fold greater than that for TPMP, as a result of its greater binding within the mitochondrial matrix. DecylTPP was also taken up extensively by cells, indicating that increased hydrophobicity enhanced uptake. Both MitoQ and DecylTPP were taken up very rapidly into cells, reaching a steady state within 15 min, compared with approximately 8 h for TPMP. This far faster uptake was the result of the increased rate of passage of hydrophobic TPP molecules through the plasma membrane. Within cells MitoQ was predominantly located within mitochondria, where it was rapidly reduced to the ubiquinol form, consistent with its protective effects in cells and in vivo being due to the ubiquinol antioxidant. The strong influence of hydrophobicity on TPP cation uptake into mitochondria within cells facilitates the rational design of mitochondria-targeted compounds to report on and modify mitochondrial function in vivo.
Authors:
Meredith F Ross; Tracy A Prime; Irina Abakumova; Andrew M James; Carolyn M Porteous; Robin A J Smith; Michael P Murphy
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  411     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-09     Completed Date:  2008-04-25     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  633-45     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
Cations / chemistry,  metabolism
Cell Membrane / metabolism*
Fibroblasts
Humans
Hydrophobic and Hydrophilic Interactions*
Jurkat Cells
Mitochondria, Liver / metabolism*
Molecular Structure
Onium Compounds / chemistry,  metabolism*
Oxidation-Reduction
Rats
Time Factors
Trityl Compounds / chemistry,  metabolism*
Grant Support
ID/Acronym/Agency:
MC_U105663142//Medical Research Council; //Medical Research Council
Chemical
Reg. No./Substance:
0/Cations; 0/Onium Compounds; 0/Trityl Compounds; 15912-74-0/triphenylmethylphosphonium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Cooperation of photosystem I with the plastoquinone pool in oxygen reduction in higher plant chlorop...
Next Document:  Cep57, a multidomain protein with unique microtubule and centrosomal localization domains.